In addition to being used in cancer chemotherapy, cisplatin is also known as a radiation sensitizer. That is, such that the cisplatin enhances the effect of ionizing radiation on malignant tumors in order to improve local and regional cancer treatment by radiation, see, for example, Overgaard, et al., Cancer Treatment Reports Vol. 65, Nos. 5-6, May/June, 1981, p. 501-503, which is incorporated herein by reference. There, it is reported that cisplatin will enhance the radiation response in tumors by a factor of between 1.2 and 1.7 times the effectiveness if no cisplatin is used. The report goes on to describe the use of cisplatin as a marked and selective enhancement of radiation's effects in solid tumors. Cisplatin has the formula: ##STR1## The technical chemical name for cisplatin is cis-diaminedichloroplatinum(II). It is a square planar molecule and its effectiveness in biological systems is believed to be related to its configuration. The compound was recognized for its biological significance in the 1960's and its radiation sensitizing properties were demonstrated in the mid-1970's.
While cisplatin per se has been known as an effective radiation sensitizer, it does have problems which have inhibited its practical use. The primary problem is its high level of toxicity to normal living cells. Thus, while it may successfully sensitize a carcinoma, making it highly susceptible to radiation treatment, it also is quite toxic to the surrounding normal cells. There is, therefore, a real and continuing need to develop a radiation sensitizer which is at least equally as effective as cisplatin with respect to the enhancement of sensitivity of carcinomas to radiation, but which will allow such sensitization without being toxic to surrounding normal living cells.
Needless to say, if one could develop a radiation sensitizer of high level sensitizing effect, but with minimal toxicity to surrounding normal living cells, the net effect would be that smaller doses of radiation could be used to give the effect now achieved with only larger radiation doses and thus, the total body exposure to radiation reduced. Alternatively, for a given radiation dose, its effectiveness could be increased without fear of causing high level toxicity to surrounding normal tissue cells.
It is a primary objective of the present invention to provide a radiation sensitizer which is at least equal to cisplatin in selective enhancement of radiation response, but which provides such radiation response with a much, much lower toxicity level to normal live cells.
An additional objective of the present invention is to provide a radiation sensitizer which is at least equal to cisplatin in enhancement of radiation response, but which is several times less toxic than cisplatin to normal living cells.
A further objective of this invention is to provide a radiation sensitizer which is at least equal to cisplatin in radiation sensitization effect, but which is estimated to be up to ten times less toxic to normal cells.
Another object is to provide a compound which like cisplatin itself has antineoplastic properties.
A still further objective of the present invention is to provide a molecular tracer which is fluorescent, thus providing a unique and highly effective biological tracer which is capable of binding to DNA nucleotides, proteins, and lipids.
Yet another objective of this invention is to provide a fluorescent biological tracer which also will function as an effective biological stain for use in electron microscopy and fluorescence microscopy.
Still another objective of the present invention is to provide a radiation sensitizer that has stability and solubility properties which make the compounds easy to administer in dosage quantity.
And another objective of the present invention is to provide a radiation sensitizer which is soluble in water and soluble in common universal solvents such as dimethylsulfoxide, methyl alcohol, ethyl alcohol, acetone, etc.
Another very important objective of the present invention is to provide a highly effective, single step synthesis for production of fluorescently labeled cisplatin type compounds, which do not employ cisplatin at all in the synthesis procedure, but instead employ readily available compounds in a single step, direct combination synthesis.
The method and manner of accomplishing each of the above objectives, as well as others, will become apparent from the detailed description of the invention which follows hereinafter.